1. Field of the Invention
The present invention relates to preparation of microparticles. More particularly, the present invention relates to apparatus and methods for preparing microparticles using liquid extraction of solvent in the emulsion.
2. Related Art
Various methods are known that can encapsulate compounds in the form of microparticles. It is particularly advantageous to encapsulate a biologically active or pharmaceutically active agent within a biocompatible, biodegradable wall forming material (e.g., a polymer) to provide sustained or delayed release of drugs or other active agents. In emulsion-based methods, the material to be encapsulated (drugs or other active agents) is generally dissolved, dispersed, or emulsified in a solvent containing the wall forming material to form a discontinuous phase. The discontinuous phase is combined with a continuous phase to form an emulsion. Solvent is then removed from the emulsion droplets to form the hardened microparticle product.
One approach to solvent removal is to evaporate the solvent, such as by vacuum or heating. One drawback of solvent removal through evaporation is the length of time that is required to remove a sufficient quantity of solvent so that any remaining residual solvent is at an acceptably safe level for use of the microparticles by humans and other animals. The length of time for solvent removal through evaporation can be reduced somewhat by using aqueous extraction of solvent in conjunction with solvent evaporation. An example of such a combined evaporative and aqueous extraction process is described in U.S. Pat. No. 4,389,330. However, such a combined evaporative and aqueous extraction process is not suitable, much less optimal, for solvents that are not amenable to evaporation, such as benzyl alcohol.
Other conventional emulsion-based processes for preparing microparticles rely solely on aqueous extraction of solvent, such as the process described in U.S. Pat. No. 5,407,609. One drawback of aqueous extraction of solvent is the large volume of water that is required. As noted in U.S. Pat. No. 5,407,609, the volume of the extraction medium should be at least the volume needed to dissolve all of the solvent out of the emulsion droplets, such as a volume 10-fold or higher. This problem is particularly acute when the microparticles are being prepared on a commercial scale. Larger and/or more equipment is required to accommodate the large volume of water in the process, resulting in higher equipment and disposal costs.
Thus, there is a need in the art for an improved method and apparatus for preparing microparticles. There is a particular need in the art for an improved process of solvent removal that overcomes the drawbacks of conventional evaporative and aqueous extraction techniques. The present invention, the description of which is fully set forth below, solves the need in the art for such a method and apparatus.